The Dependence of Hydrophobic Interactions on the Shape of Solute Surface.

According to our recent studies on hydrophobicity, this work is aimed at understanding the dependence of hydrophobic interactions on the shape of a solute's surface. It has been observed that dissolved solutes primarily affect the structure of interfacial water, which refers to the top layer of water at the interface between the solute and water. As solutes aggregate in a solution, hydrophobic interactions become closely related to the transition of water molecules from the interfacial region to the bulk water. It is inferred that hydrophobic interactions may depend on the shape of the solute surface. To enhance the strength of hydrophobic interactions, the solutes tend to aggregate, thereby minimizing their surface area-to-volume ratio. This also suggests that hydrophobic interactions may exhibit directional characteristics. Moreover, this phenomenon can be supported by calculated potential mean forces (PMFs) using molecular dynamics (MD) simulations, where different surfaces, such as convex, flat, or concave, are associated with a sphere. Furthermore, this concept can be extended to comprehend the molecular packing parameter, commonly utilized in studying the self-assembly behavior of amphiphilic molecules in aqueous solutions.

Unveiling the Stacking Fault-Driven Phase Transition Delaying Cryogenic Fracture in Fe-Co-Cr-Ni-Mo-C-Based Medium-Entropy Alloy.

In this work, the tensile deformation mechanisms of the Fe55Co17.5Cr12.5Ni10Mo5-xCx-based medium-entropy alloy at room temperature (R.T.), 77 K, and 4.2 K are studied. The formation of micro-defects and martensitic transformation to delay the cryogenic fracture are observed. The results show that FeCoCrNiMo5-xCx-based alloys exhibit outstanding mechanical properties under cryogenic conditions. Under an R.T. condition, the primary contributing mechanism of strain hardening is twinning-induced plasticity (TWIP), whereas at 77 K and 4.2 K, the activation of martensitic transformation-induced plasticity (TRIP) becomes the main strengthening mechanism during cryogenic tensile deformation. Additionally, the carbide precipitation along with increased dislocation density can significantly improve yield and tensile strength. Furthermore, the marked reduction in stacking fault energy (SFE) at cryogenic temperatures can promote mechanisms such as twinning and martensitic transformations, which are pivotal for enhancing ductility under extreme conditions. The Mo4C1 alloy obtains the optimal strength-ductility combination at cryogenic-to-room temperatures. The tensile strength and elongation of the Mo4C1 alloy are 776 MPa and 50.5% at R.T., 1418 MPa and 71.2% in liquid nitrogen 77 K, 1670 MPa and 80.0% in liquid helium 4.2 K, respectively.

Psychological impact of the COVID-19 pandemic on infertile patients: A systematic review and meta-analysis.

The present study aimed to examine the psychological impact of the COVID-19 pandemic on infertile patients. We adopted a comparison design and searched articles published from 1 September 2016 to 31 December 2019 as the control group, while articles published from 1 January 2020 to 31 April 2023 were treated as the pandemic group. Specifically, Web of Science, PubMed, Medline, PsycArticle, CNKI and PsycINFO were searched to identify potential eligible records. Risk of bias was assessed, and random-effects meta-analyses were conducted to estimate the prevalence of specific mental health problems. Forty studies with a total of 19,480 participants were included in the analysis. The pooled prevalence of anxiety in the pandemic group was significantly higher than that in the control group. The depression and stress prevalence in the pandemic group was higher than that in the control group, yet did not reach statistical significance. A subgroup analysis revealed region differences with developed countries exhibiting higher rates of anxiety and depression in the pandemic group, but the result was the opposite in the control group. Physiological factors, psychological factors and social factors correlated with infertile patients' mental health were identified. The COVID-19 pandemic had a significant negative impact on infertile patients' mental health, emphasizing the importance of ways to mitigate the risks during the pandemic.

Association of sudden sensorineural hearing loss with meteorological factors: a time series study in Hefei, China, and a literature review.

Air pollution can cause disease and has become a major global environmental problem. It is currently believed that air pollution may be related to the progression of SSNHL. As a rapidly developing city in recent years, Hefei has serious air pollution. In order to explore the correlation between meteorological variables and SSNHL admissions, we conducted this study. This study investigated the short-term associations between SSNHL patients admitted to the hospital and Hefei climatic variables. The daily data on SSNHL-related hospital admissions and meteorological variables containing mean temperature (T-mean; °C), diurnal temperature range (DTR; °C), atmospheric pressure (AP; Hp), and relative humidity (RH; %), from 2014 to 2021 (2558 days), were collected. A time-series analysis integrating distributed lag non-linear models and generalized linear models was used. PubMed, Embase, Cochrane Library, and Web of Science databases were searched. Literature published up to August 2023 was reviewed to explore the potential impact mechanisms of meteorological factors on SSNHL. The mechanisms were determined in detail, focusing on wind speed, air pressure, temperature, humidity, and air pollutants. Using a median of 50.00% as a baseline, the effect of exceedingly low T-mean in the single-day hysteresis effect model began at a lag of 8 days (RR = 1.032, 95% CI: 1.001 ~ 1.064). High DTR affected the admission rate for SSNHL on lag 0 day. The significance of the effect was the greatest on that day (RR = 1.054, 95% CI: 1.007 ~ 1.104) and then gradually decreased. High and exceedingly high RH affected the admission rate SSNHL on lag 0 day, and these effects lasted for 8 and 7 days, respectively. There were significant associations between all grades of AP and SSNHL. This is the first study to assess the effect of meteorological variables on SSNHL-related admissions in China using a time-series approach. Long-term exposures to high DTR, RH values, low T-mean values, and all AP grades enhance the incidence of SSNHL in residents. Limiting exposure to extremes of ambient temperature and humidity may reduce the number of SSNHL-related hospital visits in the region. It is advisable to maintain a suitable living environment temperature and avoid extreme temperature fluctuations and high humidity. During periods of high air pollution, it is recommended to stay indoors and refrain from outdoor exercise.

Characterization and the first complete genome sequence of a novel strain of Bergeyella porcorum isolated from pigs in China.

BACKGROUND: Bergeyella porcorum is a newly identified bacterium that has an ambiguous relationship with pneumonia in pigs. However, few studies have adequately characterized this species. RESULTS: In this study, we analyzed the morphological, physiological, and genomic characteristics of the newly identified B. porcorum sp. nov. strain QD2021 isolated from pigs. The complete genome sequence of the B. porcorum QD2021 strain consists of a single circular chromosome (2,271,736 bp, 38.51% G + C content), which encodes 2,578 genes. One plasmid with a size of 70,040 bp was detected. A total of 121 scattered repeat sequences, 319 tandem repeat sequences, 4 genomic islands, 5 prophages, 3 CRISPR sequences, and 51 ncRNAs were predicted. The coding genes of the B. porcorum genome were successfully annotated across eight databases (NR, GO, KEGG, COG, TCDB, Pfam, Swiss-Prot and CAZy) and four pathogenicity-related databases (PHI, CARD, VFDB and ARDB). In addition, a comparative genome analysis was performed to explore the evolutionary relationships of B. porcorum QD2021. CONCLUSIONS: To our knowledge, this is the first study to provide fundamental phenotypic and whole-genome sequences for B. porcorum. Our results extensively expand the current knowledge and could serve as a valuable genomic resource for future research on B. porcorum.

Fast Learning of Signed Distance Functions From Noisy Point Clouds Via Noise to Noise Mapping.

Learning signed distance functions (SDFs) from point clouds is an important task in 3D computer vision. However, without ground truth signed distances, point normals or clean point clouds, current methods still struggle from learning SDFs from noisy point clouds. To overcome this challenge, we propose to learn SDFs via a noise to noise mapping, which does not require any clean point cloud or ground truth supervision. Our novelty lies in the noise to noise mapping which can infer a highly accurate SDF of a single object or scene from its multiple or even single noisy observations. We achieve this by a novel loss which enables statistical reasoning on point clouds and maintains geometric consistency although point clouds are irregular, unordered and have no point correspondence among noisy observations. To accelerate training, we use multi-resolution hash encodings implemented in CUDA in our framework, which reduces our training time by a factor of ten, achieving convergence within one minute. We further introduce a novel schema to improve multi-view reconstruction by estimating SDFs as a prior. Our evaluations under widely-used benchmarks demonstrate our superiority over the state-of-the-art methods in surface reconstruction from point clouds or multi-view images, point cloud denoising and upsampling.

K+-Specification with Flavone P0 Probe in a G-Quadruplex DNA.

G-quadruplex (G4) DNA is considered as a prospective therapeutic target due to its potential biological significance. To understand G4 biological roles and function, a G4-specific fluorescent probe is necessary. However, it is difficult for versatile G4 to precisely recognize without perturbing their folding dynamics. Herein, we reported that flavone P0 can be a fluorescent probe for G4 DNA-specific recognition and have developed a highly selective detection of K+ ion by dimeric G4/P0 system. When comparing various nucleic acid structures, including G4, i-motif, ss/ds-DNA, and triplex, an apparent fluorescence enhancement is observed in the presence of G4 DNA for 85-fold, but only 8-fold for non-G4 DNA. Furthermore, based on fluorescent probe of flavone P0 for G4 DNA screening, the noncovalent dimeric G4/P0 system is exploited as a K+ sensor, that selectively responds to K+ with a 513-fold fluorescence enhancement and a detection range for K+ ion concentration from 0 to 500 mM. This K+ sensor also has a remarkably anti-interference ability for other metal cations, especially for a high concentration of Na+. These results have demonstrated that flavone P0 is an efficient tool for monitoring G-quadruplex DNA and endows flavone P0 with bioanalytical and medicinal applications.

Type-printable photodetector arrays for multichannel meta-infrared imaging.

Multichannel meta-imaging, inspired by the parallel-processing capability of neuromorphic computing, offers considerable advancements in resolution enhancement and edge discrimination in imaging systems, extending even into the mid- to far-infrared spectrum. Currently typical multichannel infrared imaging systems consist of separating optical gratings or merging multi-cameras, which require complex circuit design and heavy power consumption, hindering the implementation of advanced human-eye-like imagers. Here, we present printable graphene plasmonic photodetector arrays driven by a ferroelectric superdomain for multichannel meta-infrared imaging with enhanced edge discrimination. The fabricated photodetectors exhibited multiple spectral responses with zero-bias operation by directly rescaling the ferroelectric superdomain instead of reconstructing the separated gratings. We also demonstrated enhanced and faster shape classification (98.1%) and edge detection (98.2%) using our multichannel infrared images compared with single-channel detectors. Our proof-of-concept photodetector arrays simplify multichannel infrared imaging systems and offer potential solutions in efficient edge detection in human-brain-type machine vision.

The genetic relationships between immune cell traits, circulating inflammatory proteins and preeclampsia/eclampsia.

Objectives: Preeclampsia/eclampsia (PE), a critical complication during pregnancy, has been suggested to correlate with immune cell phenotypes and levels of circulating inflammatory proteins. Our study aimed to employ a two-sample mendelian randomization (MR) analysis to assess the potential causal effects of immune cell phenotypes and circulating inflammatory proteins on the onset of PE. Methods: We utilized summary-level data from genome-wide association studies (GWAS). This included statistics for 371 immune cell phenotypes from 3,757 individuals in the Sardinian founder population, and data on 91 circulating inflammatory proteins from 14,824 European ancestry participants. Additionally, genetic associations related to PE were extracted from the FinnGen consortium, involving 1,413 cases and 287,137 controls. We applied inverse variance weighting (IVW) and supplementary methods like MR-Egger, weighted median, and weighted mode to comprehensively assess potential causal links. Results: Our analysis revealed significant causal associations of several immune cells type and inflammatory proteins with PE. Out of the immune cell phenotypes analyzed, six immune phenotypes emerged as significant risk factors (p <0.01), mainly include CD4 on activated and secreting CD4 regulatory T cells, CD28 on CD39+ CD4+ T cells, CD127- CD8+ T cell absolute cell (AC) counts, HLA DR on HLA DR+ CD8+ T cell, CD66b on CD66b++ myeloid cells, and HLA DR on dendritic cells. And ten were identified as protective factors (p <0.01). Such as CD45 on CD33br HLA DR+ CD14-, CD33+ HLA DR+ AC, CD33+ HLA DR+ CD14- AC, CD33+ HLA DR+ CD14dim AC, CD27 on CD24+ CD27+ B cell, CD20- CD38- %B cell, IgD- CD24- %B cell CD80 on plasmacytoid DC, CD25 on CD4+ T cell, and CD25 on activated & secreting CD4 regulatory T cell. Furthermore, among the inflammatory proteins studied, five showed a significant association with PE, with three offering protective effects mainly include that C-X-C motif chemokine 1, tumor necrosis factor ligand superfamily member 14, and C-C motif chemokine 19 and two exacerbating PE risk such as STAM-binding domain and Interleukin-6 (p <0.05). Conclusions: Our study highlights the pivotal roles played by diverse immune cell phenotypes and circulating inflammatory proteins in the pathophysiology of PE. These findings illuminate the underlying genetic mechanisms, emphasizing the criticality of immune regulation during pregnancy. Such insights could pave the way for novel intervention strategies in managing PE, potentially enhancing maternal and neonatal health outcomes.

Identification of a ferroptosis-related prognostic signature and validation of ITGA6-AS1 in enhancing cell proliferation, migration and invasion in glioma.

Glioma is the most common malignant tumor of the adult central nervous system. In this study, we aimed to identify a novel model for predicting glioma prognosis and a potential therapeutic target. Here, lncRNAs related to prognosis and ferroptosis were analyzed and screened through R software and online websites. A nomogram model was established and evaluated with calibration curve, receiver operating characteristic curve and decision curve analysis. Further, an enrichment analysis and immune infiltration analysis were performed. In addition, the expression level and biological function of ITGA6-AS1 were verified in vitro. We obtained a ferroptosis-related 7-lncRNA signature, and constructed a nomogram prognostic model with good predictability for 1-, 3- and 5-year overall survival of glioma patients. The enrichment analysis indicated potential involvement of certain pathways and suggested a correlation between the high-risk group and infiltration of M2 macrophages and MDSCs. Furthermore, the expression level of ITGA6-AS1 in the U118, U87, and LN229 cells was upregulated compared to the H1800 cell. Interestingly, knockdown of ITGA6-AS1 may inhibit U118 cells' proliferation, migration and invasion in vitro. while overexpression of ITGA6-AS1 in LN229 cells plays a promoting role. This study implies that the 7-lncRNA signature may contribute to the stratification of glioma prognosis, and the immune suppressive microenvironment may be associated with macrophage-ferroptosis crosstalk. Furthermore, ITGA6-AS1 may be a potential therapeutic target for patients with glioma.

Physiological and genetic responses of the benthic dinoflagellate Prorocentrum lima to polystyrene microplastics.

Microplastics are well known as contaminants in marine environments. With the development of biofilms, most microplastics will eventually sink and deposit in benthic environment. However, little research has been done on benthic toxic dinoflagellates, and the effects of microplastics on benthic dinoflagellates are unknown. Prorocentrum lima is a cosmopolitan toxic benthic dinoflagellate, which can produce a range of polyether metabolites, such as diarrhetic shellfish poisoning (DSP) toxins. In order to explore the impact of microplastics on marine benthic dinoflagellates, in this paper, we studied the effects of polystyrene (PS) on the growth and toxin production of P. lima. The molecular response of P. lima to microplastic stress was analyzed by transcriptomics. We selected 100 nm, 10 µm and 100 µm PS, and set three concentrations of 1 mg L-1, 10 mg L-1 and 100 mg L-1. The results showed that PS exposure had limited effects on cell growth, but increased the OA and extracellular polysaccharide content at high concentrations. After exposure to PS MPs, genes associated with DSP toxins synthesis, carbohydrate synthesis and energy metabolism, such as glycolysis, TCA cycle and pyruvate metabolism, were significantly up-regulated. We speculated that after exposure to microplastics, P. lima may increase the synthesis of DSP toxins and extracellular polysaccharides, improve the level of energy metabolism and gene expression of ABC transporter, thereby protecting algal cells from damage. Our findings provide new insights into the effects of microplastics on toxic benthic dinoflagellates.

The Impact of Social Support on Sleep Quality in Elderly Care Institutions in Northeast China: the Chain-Mediating Effect of Psychological Adjustment and Coping Style.

Purpose: The aim of this study was to investigate the sleep quality as well as the influence of social support on the sleep quality of elderly people in nursing homes in northeast China, and analyze the chain-mediating role of psychological adjustment and coping styles in social support and sleep quality, thereby to provide a scientific basis for the development of effective intervention measures in this direction. Patients and Methods: This study was conducted during January-March 2023 and adopted a cluster sampling method to select 5 elderly care institutions from across the Jilin, Liaoning, and Heilongjiang provinces in Northeast China. A questionnaire survey was conducted using the Self-mate General Situation Questionnaire, Pittsburgh Sleep Quality Index, Nursing Home Adjustment Scale for the Elderly, Social Support Rating Scale, and Medical Coping Modes Questionnaire. Statistical analysis methods, including ANOVA, logistic multi-factor regression, and Pearson's correlation were employed in SPSS 26.0, while Amos 26.0 was used to build a structural equation model to analyze the interaction path and the mediating role between the variables. Results: The sleep quality of elderly individuals in elderly care institutions was relatively low 8.43(3.456). Social support of elderly individuals in elderly care institutions affected their sleep quality through i) both psychological adjustment and face-to-face coping style (B = 0.493, P < 0.001, 95% CI = 0.050-0.122) and ii) both psychological adjustment and avoidance coping style (B = -0.302, P < 0.001, 95% CI = -0.119 to -0.048). Psychological adjustment, confrontation coping, and avoidance coping played a mediating role in the sequential relationship between social support and the sleep quality of elderly individuals in elderly care institutions. Conclusion: Psychological adjustment and coping styles have a chain-mediating effect between social support and sleep quality of the elderly in northeast China's elderly care institutions.

Association of traditional and novel obesity indicators with stroke risk: Findings from the Rural Chinese cohort study.

BACKGROUND AND AIMS: Few researchers have compared the effectiveness of traditional and novel obesity indicators in predicting stroke incidence. We aimed to evaluate the associations between six obesity indices and stroke risk, and to further identify the optimal indicator. METHODS AND RESULTS: A total of 14,539 individuals from the Rural Chinese Cohort Study were included in the analyses. We used the Cox proportional hazards regression models to evaluate the association between six obesity indices (including body mass index [BMI], waist circumference [WC], conicity index [C-index], lipid accumulation product [LAP], visceral adiposity index [VAI], and Chinese visceral adiposity index [CVAI]) and stroke risk. Receiver operating characteristic curves were employed to compare their predictive ability on stroke risk. During a median follow-up period of 11.13 years, a total of 1257 cases of stroke occurred. In the multiple-adjusted Cox regression model, WC, BMI, C-index, and CVAI were positively associated with ischemic stroke (P < 0.01) rather than hemorrhagic stroke risk. Dose-response analyses showed a linear correlation of WC, BMI, C-index, and LAP (Poverall <0.05, and Pnonlinear >0.05), but a non-linear correlation of CVAI (Poverall <0.05, and Pnonlinear <0.05) with the risk of ischemic stroke. CVAI demonstrates the highest areas under the curves (AUC: 0.661, 95% CI: 0.653-0.668), indicating a superior predictive ability for ischemic stroke occurrence compared to other five indices (P < 0.001). CONCLUSION: WC, BMI, C-index, LAP, and CVAI were all positively related to the risk of ischemic stroke, among which CVAI exhibited stronger predictive ability for ischemic stroke.

Topical and oral peroxisome proliferator-activated receptor-α agonist ameliorates diabetic corneal neuropathy.

Diabetic corneal neuropathy (DCN) is a common diabetic ocular complication with limited treatment options. In this study, we investigated the effects of topical and oral fenofibrate, a peroxisome proliferator-activated receptor-α agonist, on the amelioration of DCN using diabetic mice (n = 120). Ocular surface assessments, corneal nerve and cell imaging analysis, tear proteomics and its associated biological pathways, immuno-histochemistry and western blot on PPARα expression, were studied before and 12 weeks after treatment. At 12 weeks, PPARα expression markedly restored after topical and oral fenofibrate. Topical fenofibrate significantly improved corneal nerve fibre density (CNFD) and tortuosity coefficient. Likewise, oral fenofibrate significantly improved CNFD. Both topical and oral forms significantly improved corneal sensitivity. Additionally, topical and oral fenofibrate significantly alleviated diabetic keratopathy, with fenofibrate eye drops demonstrating earlier therapeutic effects. Both topical and oral fenofibrate significantly increased corneal ß-III tubulin expression. Topical fenofibrate reduced neuroinflammation by significantly increasing the levels of nerve growth factor and substance P. It also significantly increased ß-III-tubulin and reduced CDC42 mRNA expression in trigeminal ganglions. Proteomic analysis showed that neurotrophin signalling and anti-inflammation reactions were significantly up-regulated after fenofibrate treatment, whether applied topically or orally. This study concluded that both topical and oral fenofibrate ameliorate DCN, while topical fenofibrate significantly reduces neuroinflammation.

Plasma irisin associations with executive function among children in a prospective cohort.

OBJECTIVE: To examine the longitudinal associations between irisin and executive function among children, as well as the sex difference in this correlation. METHODS: The study involving 330 children aged 6-10 years conducted in Guangzhou, China. Baseline surveys and fasting blood samples were collected in 2017. Plasma irisin concentration was measured using Enzyme-Linked Immunosorbent Assay (ELISA). Executive function was assessed by the Behavior Rating Inventory of Executive Function (BRIEF) scale in 2017 and followed up after 2 years. Multivariable linear regression was used for association analysis. RESULTS: The plasma irisin concentration was 9.04±2.18 ng/mL. There was no statistical difference in plasma irisin and change values of BRIEF T-scores between boys and girls. No significant associations were found between plasma irisin and change values of BRIEF T-scores (P > 0.05) in the overall sample. Further subgroup analyses according to sex revealed that plasma irisin was negatively associated with change values of behavior regulation index (BRI, ß=-0.521, 95 %CI: -1.036 ∼ -0.006), emotional control (ß=-0.649, 95 %CI: -1.249 ∼ -0.049), working memory T-scores (ß=-0.774, 95 %CI: -1.350 ∼ -0.199) in girls. Moreover, we firstly identified a sex effect modification in the association of plasma irisin with change values of working memory T-score (Pinterference=0.012). CONCLUSIONS: Higher irisin concentration was associated with better executive function performance in girls. Further studies that included populations in other regions or countries are needed to confirm these findings.

Sustainable double-synergistic silver-hydroxyapatite composite catalyst derived from fish bones for efficient disinfection of Vibrio parahaemolyticus.

Vibrio parahaemolyticus is a food-borne pathogen that poses a serious threat to seafood safety and human health. An efficient, nontoxic, and sustainable disinfection material with a stable structure is urgently needed. Herein, silver (Ag)-hydroxyapatite (HAP) composite catalysts were prepared using HAP derived from waste fish bones. The Ag2.50%-HAP showed a 100% disinfection rate against V. parahaemolyticus, disinfecting nearly 7.0 lg CFU mL-1 within 15 min at a low concentration of 300 µg mL-1. This efficient disinfection activity could be attributed to the double-synergistic effect of Ag and superoxide radicals, which resulted in the destruction of bacterial cell structures and the leakage of intracellular proteins. Importantly, the composite also exhibited high activity in controlling the growth of pathogens during the storage process of Penaeus vannamei. These findings provided sustainable composite catalysts for disinfecting V. parahaemolyticus in seafood and a high-value utilization strategy for waste fish bones.

Can stable carbon isotope fingerprints be competent for geographic traceability of rice?

This study aimed to improve the traceability of rice-producing areas to address the increasing demand for accurate methods to confirm food quality and safety. Compound-specific δ13C of fatty acids, δ13C of starch and bulk of rice were measured. PCA, PLS-DA and VIP value analysis of the obtained data were performed to track the source of rice from the six regions. The PLS-DA model established with bulk δ13C, starch δ13C, and fatty acid δ13C, which clearly separated the rice from six regions. The VIP graph showed the value of starch, C18:0 and C18:2 δ13C values (VIP > 1) were important to distinguish the origin of rice. Also, according to loading plots the contribution of starch δ13C was the largest. The findings indicate that the introduction of starch δ13C improves the precision of rice traceability and provides an effective method for identifying rice origin.

A generic causality-informed neural network (CINN) methodology for quantitative risk analytics and decision support.

In this paper, we develop a generic framework for systemically encoding causal knowledge manifested in the form of hierarchical causality structure and qualitative (or quantitative) causal relationships into neural networks to facilitate sound risk analytics and decision support via causally-aware intervention reasoning. The proposed methodology for establishing causality-informed neural network (CINN) follows a four-step procedure. In the first step, we explicate how causal knowledge in the form of directed acyclic graph (DAG) can be discovered from observation data or elicited from domain experts. Next, we categorize nodes in the constructed DAG representing causal relationships among observed variables into several groups (e.g., root nodes, intermediate nodes, and leaf nodes), and align the architecture of CINN with causal relationships specified in the DAG while preserving the orientation of each existing causal relationship. In addition to a dedicated architecture design, CINN also gets embodied in the design of loss function, where both intermediate and leaf nodes are treated as target outputs to be predicted by CINN. In the third step, we propose to incorporate domain knowledge on stable causal relationships into CINN, and the injected constraints on causal relationships act as guardrails to prevent unexpected behaviors of CINN. Finally, the trained CINN is exploited to perform intervention reasoning with emphasis on estimating the effect that policies and actions can have on the system behavior, thus facilitating risk-informed decision making through comprehensive "what-if" analysis. Two case studies are used to demonstrate the substantial benefits enabled by CINN in risk analytics and decision support.